• Toxicological Research
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• v.17 no.1
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• pp.17-25
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• 2001

Korean ginseng products have been fumigated with ethylene oxide (EO) for sterilization and prolongation of storage periods. However, there had been controversies indicating that consumption of EO treated foods might cause harmful effects in human. In Korea, the use EO gas for sterilization of food was banned in 1991. Since then, irradiation technique has been developed as an alternative. This study was carried out to evaluate the safety of irradiated ginseng on peri- and postnatal developmental toxicity in rats. Either EO gas fumigated or gamma-irradiated ginseng was administered to pregnant Wistar rats by oral gavage from gestational day 16 to postnatal day 21. The amount of irradiation used in this study was 5, 10 and 30 kGy, respectively. There were no treatment related changes of dams in deaths, clinical signs, and parturition. No treatment related changes in food consumption, body/organ weight and lactation of dams were observed. Also, no F1 fetuses in external abnormality, physical development, reflex/sensory junctions and behavioral development were found. The results of this study showed that gamma-irradiated ginseng, up to 30 kGy, has no adverse effects on the peri- and postnatal development of rats.

• Toxicological Research
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• v.3 no.1
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• pp.55-63
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• 1987

A Peri-and Postnatal Study was Carried out to examine the effects of rHuIFN-${\alpha}A$, produced by gene-manipulated E. coli, on offsprings of Wistar rats. The substance was administered intraperitoneally to dams at dose levels of $1{\times}10^5$, $4{\times}10^5$ and $1.2{\times}10^6$ I.U/kg/day during the period from day 17 of gestation to day 21 after delivery. All the pregnant dams were allowed to deliver naturally, and the postnatal development of the offsprings was observed. No noticeable toxic effects and pathological changes on dams were observed, and no detectable variations in postnatal development of offsprings occured.

• Toxicological Research
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• v.9 no.1
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• pp.107-118
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• 1993

LBD-007, a newly developed recombinant human interferon alphaA, was at dose levels of 0.3 $\times$$10^6$ , 6 $\times$ $10^6$ and 12 $\times$ $10^6$ IU/kg/day administered subcutaneously to pregnant and subsequent delivered SpragueDawley rats from day 17 of gestation through day 21 of lactation. Effects of test substance on dams and growth, behaviour and mating performance of F1 offspring were examined. 1. No treatmene-related changes in clinical signs, food consumption, body weight, pregnant period and necropsy findings were observed in dams.

• Biomolecules & Therapeutics
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• v.6 no.1
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• pp.73-81
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• 1998

Pregnant Sprague-Dawley rats were administered with Q-35 at the dose levels of 0, 30, 100 and 300 mg/kg/day by oral gavage from gestation day 17 to lactation period. Effects of the test chemical on general findings, reproductive performance of dams and development of Fl generation were examined. There were no treatment related changes in physical signs, body weight, necropsy findings, organ weights, delivery and nursing behavior. In 100 and 300 mg/fg/day treated groups, the food consumption of dams was decreased significantly during gestational day 19~21. The gestation length of 300 mg/tg/day treated group was increased significantly compared to the control group (22.3 $\pm$0.48 vs 22.0$\pm$0.39). Although the gestational length of all groups were in normal range of the rat, potential effect of the drug could not be ruled out. External anomaly of Fl fetus induced by Q-35 was not detected in any groups. There were no treaoent related changes in physical development, reflex functions, sensory functions, locomotor activity and motor coordinating activity. Estrus cycle, fertility and reproductive performance of Fl were not changed in all treated groups. There was no external abnormality related to the drug administration on the examination of F2. These results suggest that Q-35 has no adverse effect on the peri- and postnatal period in rats except the reduction of food consumption at the beginning of drug administration and the potential effect on the elongation of gestation length.

• Environmental Mutagens and Carcinogens
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• v.22 no.2
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• pp.125-132
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• 2002

To evaluate the modifying effect of Kwao Kreu, Pueraria mirifica (PM) well-known as a rejuvenating folk medicine from Thailand, peri- and post-natal studies were carried out in rats. PM extract was administered to pregnant Sprague Dawley (SD) rats by oral gavage from gestation 6 (GD 6) to postnatal day 21 (PND 21). The amount of administered in this study was 0.042, 0.42 and 4.2 mg/kg/day, respectively. There were no treatment related changes of dams in deaths, clinical signs, and parturition. Treatment related changes in body weight, food consumption and lactation of dams were not observed. F1 fetuses in external abnormality, physical development, reflex/sensory functions and behavioral development were not found. No adults and F1 fetuses in organ weight was found with the exception of vagina and uterus of F1 fetuses. The results showed that PM extract, up to 4.2 mg, had no adverse effects on the peri- and post-natal development of rats. Therefore, PM extract has no adverse effects on peri- and post-natal development of rats.

• Biomolecules & Therapeutics
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• v.3 no.1
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• pp.38-46
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• 1995

DA-125, a new anthracycline antitumor antibiotic, was administered at dose levels of 0, 0.04, 0.2 and 1.0 mg/kg/day intravenously to pregnant and subsequently delivered Sprague-Dawley rats from day 17 of gestation to day 21 of lactation. Effects of test agent on general toxicity of dams and growth, behaviour and mating performance of F1 offspring were examined. At 1 mg/kg, one out of the twentytwo dams showed difficult delivery, characterized by a stillbirth. Reduction in body weight, loss in food intake, and decrease in spleen weight were also observed in dams. In addition, the lower rates of successful performances in memory test (28.6%) and necrosis of tail end (9.5%) were seen in F1 offspring. At 0.04 and 0.2 mg/kg, no toxic effect on dams and F1 offspring was observed. There were no malformed Fl and F2 fetuses in all groups. The results indicate that the no effect dose levels(NOELs) of DA-125 are 0.2 mg/kg/day for dams and Fl offspring, and over 1 mg/kg/day for F2 fetuses.

• Biomolecules & Therapeutics
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• v.4 no.4
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• pp.339-348
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• 1996

A new composite antibiotic, SM-101 (sulbactam·metampicillin), was at dose levels of 0, 250, 500 and 1000 mg/kg/day administered intravenously to pregnant and subsequently delivered Sprague-Dawley rats from day 17 of gestation to day 21 of lactation. Effects of test agent on dams and growth, behaviour and mating performance of Fl offspring were examined. In dams, one death occurred at 1000 mg/kg. The increase in kidney weight of the 250, 500 and 1000 mg/kg group was found. In F1 offspring, both delayed incisors eruption and decreased body weight were observed in females of the 1000 mg/kg group. The increase in the weights of liver and kidney was found in males of the 1000 mg/kg group. No treatment-related abnormalities were observed in each treated group in terms of behaviour and reproductive performance. In F1/F2 fetuses, no drug-induced abnormalities occurred at all doses tested. The results show that the no effect dose level (NOEL) of SM-101 is under 250 mg/kg/day for dams and 500 mg/kg/day for F1 offspring, and over 1000 mg/kg/day for F1/F2 fetuses.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.6
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• pp.693-699
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• 2010

Imprinted genes are essential for fetal development, growth regulation, and postnatal behavior. However, little is known about imprinted genes in livestock. We hypothesized that certain putatively imprinted genes affected normal peri-implantation development such as embryo elongation, initial placental development, and preparation of implantation. The objective of the present study was to investigate the mRNA expression patterns of several putatively imprinted genes during the porcine peri-implantation stages from day 6 to day 21 of gestation. Imprinted genes were selected both maternally (Dlk1, IGF2, Ndn, and Sgce) and paternally (IGF2r, H19, Gnas and Xist). Here, we report that the maternally imprinted gene IGF2 was expressed from day 6 (Blastocyst stage), but Dlk1, Ndn, and Sgce were not expressed in this stage. These genes were first expressed between days 12 and day 14. All the maternally imprinted genes studied showed significantly high expression patterns from day 18 of embryo development. In contrast, paternally imprinted genes IGF2r, H19, Gnas, and Xist were first expressed from day 6 of embryo development (BL). Our data demonstrated that the expression of H19 and Gnas genes was significantly increased from day 14 of the embryo developmental stage, while IGF2r and Xist only showed high expression after day 21. This study is the first to show that the putatively imprinted genes were stage-specific during porcine embryonic development. These results demonstrate that the genes studied may exert important effects on embryo implantation and fetal development.

• Toxicological Research
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• v.29 no.1
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• pp.53-60
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• 2013

Studies on milk transfer of drugs in non-human primates (NHPs) are among the crucial components in the assessment of peri- and postnatal toxicity because of the similarity between NHPs and humans. To evaluate the milk transfer of valproic acid (VPA) in NHPs, the toxicokinetics of VPA, an antiepileptic drug, were studied in pregnant cynomolgus monkeys. VPA was administered once daily to pregnant cynomolgus monkeys at doses of 0, 30, 90, and 270 mg/kg by oral gavage from Day 100 of gestation (GD 100) to Day 31 of lactation (LD 31). Concentrations of VPA and its metabolite, 4-ene-VPA, in the maternal plasma on GD 100, GD 140, and LD 30, and concentrations of VPA and 4-ene-VPA in the offspring plasma and milk on LDs 30 and 31, respectively, were quantified using liquid chromatography tandem mass spectrometry (LC/MS/MS). After administration of a single oral dose of VPA to pregnant monkeys on GD 100, the concentrations of VPA and 4-ene-VPA were generally quantifiable in the plasma of all treatment groups up to 24 hr after administration, which showed that VPA was absorbed and that the monkeys were systemically exposed to VPA and 4-ene-VPA. After administration of multiple doses of VPA to the monkeys, VPA was detected in the pup's plasma and in milk taken on LD 30 and LD 31, respectively, which showed that VPA was transferred via milk, and the pup was exposed to VPA. Further, the concentration of VPA in the milk increased with an increase in the dose. Extremely low concentrations of 4-ene VPA were detected in the milk and in the pup plasma. In conclusion, pregnant monkeys were exposed to VPA and 4-ene-VPA after oral administration of VPA at doses of 30, 90, and 270 mg/kg/day from GD 100 to LD 31. VPA was transferred via milk, and the VPA exposure to the pup increased with an increase in the dose of VPA. The metabolite, 4-ene VPA, was present in extremely low concentrations (< 0.5 ${\mu}g/ml$) in the milk and in the pup plasma. In this study, we established methods to confirm milk transfer in NHPs, such as mating and diagnosis of pregnancy by examining gestational sac with ultrasonography, collection of milk and pup plasma and determination of toxicokinetics, using cynomolgus monkeys.